Distribution and metabolism of L-3-O-methyldopa in rats.

1. After intraperitoneal administration of L-2-(14)C-3-O-methyldopa ((14)C-O-methyldopa) to rats, the amino-acid was distributed evenly in blood, brain, heart, adipose tissue and liver, whereas it accumulated more in the kidney and the pancreas. (14)C-O-methyldopa showed a biological half-life of about 12-13 h in blood, brain and heart.2. The concentration curve of (14)C-O-methyldopa in brain (after increasing doses of the amino-acid) was linear if measured 2 h after administration, but seemed to reach a plateau at the higher doses if determined after 16 h.3. The concentrations of (14)C-O-methyldopa metabolites (mainly homovanillic acid and 4-hydroxy-3-methoxyphenyllactic acid) were low, except in the kidney, and varied according to the tissue.4. Twenty-four hours after administration of (14)C-O-methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main (14)C-homovanillic acid and (14)C-4-hydroxy-3-methoxyphenyllactic acid) and of 5% of unchanged (14)C-O-methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end-products.5. It is concluded that (14)C-O-methyldopa easily penetrates from the blood into various tissues, including brain, and that the majority of the amino-acid undergoes a slow metabolism. The different shape of the concentration curves for (14)C-O-methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino-acid.